Numerous references disclosure diltiazem in sustained release formulations which utilize microencapsulation technology. For example are the following:
U.S. Pat. No. 4,452,042, issued to Samejima et al. on Sept. 17, 1985; PA1 U.S. Pat. No. 4,462,982, issued to Samejima et al. on July 31, 1984; PA1 U.S. Pat. No. 4,443,497, issued to Samejima et al. on Apr. 17, 1984; and PA1 U.S. Pat. No. 4,411,933, issued to Samejima et al. on Oct. 25, 1983. PA1 Belgian Application No. 900,817, published on Feb. 1, 1985 discloses a device comprising a semipermeable wall, an osmopolymer, such as poly(ethylene oxide) and an active ingredient. PA1 Belgian Application No. 900,824 also published on Feb. 1, 1985 discloses a core and a membrane having variable permeability; PA1 Belgian Application No. 898,819, published May 30, 1984, discloses a device for controlled drug delivery containing two compositions including poly(ethyleneoxide); PA1 Belgian Application No. 903,540 published Feb. 17, 1986 discloses a sustained release powder, which can be formulated into an ointment, suspension etc. PA1 Belgian Application No. 901,359 published Apr. 16, 1985 discloses a controlled release diltiazem formulation containing granules and a semipermeable external membrane. PA1 Japanese Application No. 175,144 published on Apr. 13, 1984, discloses a sustained release thermoset or thermoplastic resin; PA1 Japanese Application No. 170,440 published on Apr. 5, 1984, discloses a sustained release tablet which utilizes hardened oil; PA1 Japanese Kokai No 62/5915, published Jan. 12, 1987, discloses diltiazem in combination with an acrylic acid resin; PA1 Japanese Kokai No. 61/21517, published Sept. 20, 1986 discloses the use of diltiazem in combination with hydrogenated oils; PA1 Japanese Kokai No. 59/10512 published Jan. 20, 1984, discloses microencapsulation of diltiazem, which is coated with ethylcellulose; PA1 Panoz and Geohagan, U.S. Pat. No. 4,721,619 discloses an alternating arrangement (between 50 and 200 layers) of diltiazem, organic acid and lubricant layers and polymeric material layers built upon a central inert core.
Similarly, numerous publications have disclosed devices which rely upon an osmotically regulated membrane for the controlled delivery of pharmaceuticals, such as diltiazem. For example are the following:
Schor et al., U.S. Pat. No. 4,389,393 discloses a sustained release tablet which is one or more hydroxypropylmethylcellulose or a mixture of one or more hydroxypropylmethylcelluloses and up to 30% by weight of the mixture of methylcellulose, sodium carboxymethylcellulose and/or other cellulose ether, and wherein at least one of the hydroxypropylmethylcelluloses has a methoxy content of 16-24 weight-%, a hydroxypropyl content of 4-32 weight-% and a number average molecular weight of at least 50,000 and wherein the carrier base material constitutes less than about one third of the weight of the solid unit dosage form.
However, none of the references disclose a long acting release diltiazem tablet formulation utilizing a uniformly dispersed hydrophilic matrix containing more than about 30 percent by weight of HPMC.